No study so far investigates the change of PEEP setting in prone positioning for  > 24 h. We conducted a preliminary study to examine the trend of optimal PEEP and the resulting physiological parameters in the course of prone positioning up to 42 h. The investigated parameters included Crs, mechanical power and the ratio of partial pressure of oxygen in arterial blood (PaO2) to the fraction of inspiratory oxygen concentration (FiO2). In our study, a substantial deterioration in mechanical power post-30-h proning was noted in one patient, with a concurrent drop in PaO2/FiO2 at TP36 (Fig. 1 bottom purple lines). Future investigations should explore the link between personalized proning durations, ventilator adjustments and patient outcomes such as ventilator-free days and mortality rates, aiming to provide valuable insights for clinical practice.